Prior immunity to Ureaplasma urealyticum protects against respiratory infection in immunosuppressed mice

ABSTRACT Ureaplasma species can cause systemic infections in immunocompromised hosts, including lung transplant recipients. Here, we investigated the impact of prior exposure to Ureaplasma urealyticum on the risk of U. urealyticum and Ureaplasma parvum infection in mice subjected to an immunosuppres...

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Main Authors: Maha Y. Al-Jabri, Robin Patel, Derek Fleming
Format: Article
Language:English
Published: American Society for Microbiology 2025-01-01
Series:Microbiology Spectrum
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Online Access:https://journals.asm.org/doi/10.1128/spectrum.01763-24
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author Maha Y. Al-Jabri
Robin Patel
Derek Fleming
author_facet Maha Y. Al-Jabri
Robin Patel
Derek Fleming
author_sort Maha Y. Al-Jabri
collection DOAJ
description ABSTRACT Ureaplasma species can cause systemic infections in immunocompromised hosts, including lung transplant recipients. Here, we investigated the impact of prior exposure to Ureaplasma urealyticum on the risk of U. urealyticum and Ureaplasma parvum infection in mice subjected to an immunosuppression regimen similar to that administered to solid organ transplant recipients. Mice were immunized with three intramuscular injections of U. urealyticum, with control mice injected with adjuvant only. Following immunization, mice received tacrolimus, mycophenolate mofetil, and methylprednisolone, and then were challenged with U. urealyticum or U. parvum intraperitoneally and intratracheally over 6 days. Relative U. urealyticum antibody levels in plasma were assessed over time, and lungs were harvested at sacrifice for bacterial load quantification, assessed using a color-changing unit assay. U. urealyticum antibody levels were higher in immunized compared with control animals (P < 0.0001), even when animals were immunosuppressed. U. urealyticum and U. parvum lung burden was reduced in immunized compared with control mice (~6 log10 reduction for U. urealyticum and <1 log10 reduction for U. parvum; P = 0.008 and 0.046, respectively). In summary, this study shows that prior exposure to live U. urealyticum provides some protection against infection with U. urealyticum.IMPORTANCEUreaplasma-induced hyperammonemia syndrome is a rare but potentially deadly complication of solid organ transplantation, especially lung transplantation. The pathophysiology of this relatively recently recognized condition is poorly understood, and it is unclear what factors may influence patient susceptibility. This study investigates the possible protective effects of prior exposure to Ureaplasma urealyticum in a mouse model subjected to an immunosuppression regimen similar to that given to lung transplant recipients. The findings show that prior exposure could provide protection against Ureaplasma lung infection.
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spelling doaj-art-ffc81b51be4344bba9b2b4bf8badb2782025-01-07T14:05:18ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972025-01-0113110.1128/spectrum.01763-24Prior immunity to Ureaplasma urealyticum protects against respiratory infection in immunosuppressed miceMaha Y. Al-Jabri0Robin Patel1Derek Fleming2Divisin of Public Health, Infectious Diseases, and Occupational Medicine, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USADivisin of Public Health, Infectious Diseases, and Occupational Medicine, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USADivision of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USAABSTRACT Ureaplasma species can cause systemic infections in immunocompromised hosts, including lung transplant recipients. Here, we investigated the impact of prior exposure to Ureaplasma urealyticum on the risk of U. urealyticum and Ureaplasma parvum infection in mice subjected to an immunosuppression regimen similar to that administered to solid organ transplant recipients. Mice were immunized with three intramuscular injections of U. urealyticum, with control mice injected with adjuvant only. Following immunization, mice received tacrolimus, mycophenolate mofetil, and methylprednisolone, and then were challenged with U. urealyticum or U. parvum intraperitoneally and intratracheally over 6 days. Relative U. urealyticum antibody levels in plasma were assessed over time, and lungs were harvested at sacrifice for bacterial load quantification, assessed using a color-changing unit assay. U. urealyticum antibody levels were higher in immunized compared with control animals (P < 0.0001), even when animals were immunosuppressed. U. urealyticum and U. parvum lung burden was reduced in immunized compared with control mice (~6 log10 reduction for U. urealyticum and <1 log10 reduction for U. parvum; P = 0.008 and 0.046, respectively). In summary, this study shows that prior exposure to live U. urealyticum provides some protection against infection with U. urealyticum.IMPORTANCEUreaplasma-induced hyperammonemia syndrome is a rare but potentially deadly complication of solid organ transplantation, especially lung transplantation. The pathophysiology of this relatively recently recognized condition is poorly understood, and it is unclear what factors may influence patient susceptibility. This study investigates the possible protective effects of prior exposure to Ureaplasma urealyticum in a mouse model subjected to an immunosuppression regimen similar to that given to lung transplant recipients. The findings show that prior exposure could provide protection against Ureaplasma lung infection.https://journals.asm.org/doi/10.1128/spectrum.01763-24Ureaplamsalung transplantationUreaplasma-induced hyperammonemiaimmunization
spellingShingle Maha Y. Al-Jabri
Robin Patel
Derek Fleming
Prior immunity to Ureaplasma urealyticum protects against respiratory infection in immunosuppressed mice
Microbiology Spectrum
Ureaplamsa
lung transplantation
Ureaplasma-induced hyperammonemia
immunization
title Prior immunity to Ureaplasma urealyticum protects against respiratory infection in immunosuppressed mice
title_full Prior immunity to Ureaplasma urealyticum protects against respiratory infection in immunosuppressed mice
title_fullStr Prior immunity to Ureaplasma urealyticum protects against respiratory infection in immunosuppressed mice
title_full_unstemmed Prior immunity to Ureaplasma urealyticum protects against respiratory infection in immunosuppressed mice
title_short Prior immunity to Ureaplasma urealyticum protects against respiratory infection in immunosuppressed mice
title_sort prior immunity to ureaplasma urealyticum protects against respiratory infection in immunosuppressed mice
topic Ureaplamsa
lung transplantation
Ureaplasma-induced hyperammonemia
immunization
url https://journals.asm.org/doi/10.1128/spectrum.01763-24
work_keys_str_mv AT mahayaljabri priorimmunitytoureaplasmaurealyticumprotectsagainstrespiratoryinfectioninimmunosuppressedmice
AT robinpatel priorimmunitytoureaplasmaurealyticumprotectsagainstrespiratoryinfectioninimmunosuppressedmice
AT derekfleming priorimmunitytoureaplasmaurealyticumprotectsagainstrespiratoryinfectioninimmunosuppressedmice